Several studies show that a positive cuff leak test combined with the presence of risk factors can identify patients with increased risk for laryngeal edema.. The present review will pro
Trang 1Laryngeal edema is a frequent complication of intubation It often
presents shortly after extubation as post-extubation stridor and
results from damage to the mucosa of the larynx Mucosal damage
is caused by pressure and ischemia resulting in an inflammatory
response Laryngeal edema may compromise the airway
neces-sitating reintubation Several studies show that a positive cuff leak
test combined with the presence of risk factors can identify
patients with increased risk for laryngeal edema Meta-analyses
show that pre-emptive administration of a multiple-dose regimen of
glucocorticosteroids can reduce the incidence of laryngeal edema
and subsequent reintubation If post-extubation edema occurs this
may necessitate medical intervention Parenteral administration of
corticosteroids, epinephrine nebulization and inhalation of a
helium/oxygen mixture are potentially effective, although this has
not been confirmed by randomized controlled trials The use of
non-invasive positive pressure ventilation is not indicated since this
will delay reintubation Reintubation should be considered early
after onset of laryngeal edema to adequately secure an airway
Reintubation leads to increased cost, morbidity and mortality
Introduction
Laryngeal edema is a common cause of airway obstruction
after extubation in intensive care patients and is thought to
arise from direct mechanical trauma to the larynx by the
endotracheal tube [1,2] The severity of airway obstruction
due to laryngeal edema varies In more severe cases, the
edema can lead to acute respiratory compromise
neces-sitating emergency reintubation [2-8] Reintubation itself is
associated with increased mechanical ventilation days and
length of stay in the intensive care unit, higher costs, morbidity
and mortality [5,9-12] These associations, however, do not all
apply to reintubation due to laryngeal edema
The increased attention for post-extubation laryngeal edema
is reflected by several recent studies [3,4,6-8,13-16] Some
of these studies have attempted to identify risk factors,
whereas others studied the potential preventive effect of corticosteroids on the development of clinically relevant laryngeal edema [3,4,6,7,13]
The present review will provide an overview of the etiology, incidence, risk factors, prevention and treatment of post-extubation laryngeal edema and post-extubation failure in adult critically ill patients admitted to the intensive care unit Since the incidence, pathophysiological mechanisms, conse-quences and management of laryngeal edema in children differ considerably from those in adults, discussing laryngeal edema in children is beyond the scope of this article
Etiology and pathogenesis
Endotracheal intubation can cause damage to the oro-pharynx, larynx and trachea [2,17-21] Laryngeal edema and mucosal ulcerations occur in almost all patients intubated for
4 days or more [2,19,20] Vocal cord ulceration and granu-lation tissue are also found in most cases, usually located posterior to the level of the vocal cords, where the tube exerts the highest pressure [2,18,21,22] These injuries are usually reversible, with most of the lesions resolving within 1 month [2,17,21] Pressure and ischemia are thought to contribute to mucosal edema, which may subsequently progress and present as inspiratory stridor within hours of extubation (Figure 1) [18,22,23] Quantitative data on lumen narrowing pertaining to laryngeal edema and respiratory distress are not available: however, respiratory distress develops in those patients with >50% narrowing of the tracheal lumen [24]
Incidence
Although laryngeal edema occurs in nearly all intubated patients, only some of them develop clinical symptoms Laryn-geal edema is therefore usually transient and self-limiting Clinical signs associated with laryngeal edema develop
Review
Clinical review: Post-extubation laryngeal edema and extubation failure in critically ill adult patients
Bastiaan HJ Wittekamp1, Walther NKA van Mook2, Dave HT Tjan1, Jan Harm Zwaveling2
and Dennis CJJ Bergmans2
1Department of Intensive Care, Gelderse Vallei Hospital, Willy Brandtlaan 10, 6716 RP Ede, The Netherlands
2Intensive Care Centre Maastricht, Maastricht University Medical Centre, P Debeyelaan 25, Postbus 5800, 6202 AZ Maastricht, The Netherlands
Corresponding author: Bastiaan HJ Wittekamp, icuaawittekampb@zgv.nl
This article is online at http://ccforum.com/content/13/6/233
© 2009 BioMed Central Ltd
PES = post-extubation stridor
Trang 2rapidly following extubation [25] About 15% of all
reintuba-tions are performed because of post-extubation laryngeal
edema [1] In a study by Francois and colleagues, 87 out of
611 patients (12%) developed laryngeal edema requiring
reintubation From these 87 cases, 70 (80%) patients
developed symptoms within 30 minutes after extubation,
whilst almost one-half (47%) of the patients developed
symptoms within 5 minutes [6]
Post-extubation stridor (PES) is accepted as a clinical marker
of laryngeal edema following extubation [1-3,6-9,14,25-30]
Stridor is commonly defined as a high-pitched sound
produced by airflow through a narrowed airway The ease of
clinically detecting PES, without the need for further
diag-nostic techniques, makes PES a widely used outcome
measure for post-extubation laryngeal edema
The incidence of PES varies Reported incidences vary from
3.5 to 30.2% (see Table 1) [2,3,7,8,14,25-30] Differences in
definition complicate a comparison of studies, especially
since the outcome measures used (laryngeal injury, laryngeal
edema and PES) partially overlap In the randomized
con-trolled trial of Francois and colleagues, 46% of the patients
with PES or visualized laryngeal edema in whom no medical
intervention was performed did not require reintubation The
occurrence of stridor is therefore not a very sensitive marker for
clinically relevant laryngeal edema requiring reintubation [6]
Complications
The main complication of post-extubation laryngeal edema is
reintubation The incidence of extubation failure, however,
varies widely – incidences up to 18% are reported [5,10,27] Extubation failure is often defined as reintubation within a certain time after extubation The need for reintubation may also result from other causes, however, such as pulmonary failure, heart failure, aspiration or abundant secretions [1] Several studies found reintubation rates of 1 to 4% specifi-cally due to post-extubation laryngeal edema in general inten-sive care unit populations [4-8] Reintubation rates among patients with PES are higher than in the general post-extuba-tion populapost-extuba-tion, varying from 18 to 69% [4,6,8,14,25,27,30] Reintubation in general is associated with mortality [5,9-12]
A prospective study found mortality rates of 43% in re-intubated patients, compared with a mortality of 12% in the
total study group (n = 17/40 vs n = 29/247, P < 0.00001)
[10] Morbidity is also increased due to an increased duration
of mechanical ventilation and an increased length of both intensive care unit stay and hospital stay increasing the risk for infections and other complications [10,12,31] This unfavorable outcome is reflected in the number of patients transferred to a long-term care facility (38% vs 21%,
P < 0.0001) [10] The cause of extubation failure, however,
has also been shown to be independently related to mortality [1] Airway obstruction as a cause for reintubation is associated with significantly lower mortality rates compared with nonairway reintubation causes (17.4% vs 52.9%,
P < 0.01) (Figure 2) [1].
Risk factors
Early identification of patients with an increased risk of developing laryngeal edema evolving into respiratory failure would be useful This early identification would facilitate prevention and/or early treatment Early recognition is crucial, since delay to reintubation is a predictor of hospital mortality [1]
Several studies have identified risk factors for laryngeal injury, the development of laryngeal edema or PES and the asso-ciated need for reintubation (Table 2) In general, few studies identified risk factors using multivariate analysis or correction for confounding factors [4,15,19] Female gender is a risk factor for both laryngeal edema and PES [3,4,6-8,14,25] This predisposition has been hypothesized to be due to the female mucous membrane being less resistant to trauma and thinner than that in men [4,32,33] A relatively large tube to trachea ratio in women may also facilitate mucosal injury [4,7,21,33,34], although this is not universally reported to be gender dependent [6,8]
Controversy remains in the literature about the duration of intubation and the subsequent risk of developing complications For example, the duration of intubation is identified as a risk factor for laryngeal injury by Kastanos and colleagues and by Esteller and colleagues [17,19], while Colice and colleagues and Stauffer and colleagues failed to show this relation [2,35]
Figure 1
Laryngeal edema Courtesy of L Baijens
Trang 3Early recognition of laryngeal edema is essential since these
patients have the highest risk of evolving to respiratory
distress and extubation failure Even before extubation, signs
indicative of laryngeal edema may be present
The search for a test that adequately identifies patients at
risk for extubation failure is ongoing Recently, the cuff leak
test has gained interest The test is non-invasive, relatively
easy to perform and is thought to give an indication of the patency of the upper airway When the ventilated patient is allowed to exhale with a deflated cuff, expired air normally escapes from the otherwise closed circuit The volume of leaked air can be measured by spirometry functions of the ventilator In a case of significant laryngeal edema, the lumen
of the larynx is narrowed – this results in a smaller measured air leak, and the cuff leak test will then be classified as positive (Table 3)
Table 1
Incidence of post-extubation stridor and laryngeal edema
Extubations or
Post-extubation stridor
Epstein and colleagues [1] 1998 74 11 15 Stridor with resolution upon reintubation
Maury and colleagues [25] 2004 115 4 3.5 High-pitched inspiratory wheeze within 24 hours of
extubation with respiratory rate >30/minute Sandhu and colleagues [26] 2000 110 13 11.8 High-pitched inspiratory wheeze requiring medical
intervention Miller and Cole [27] 1996 100 6 6 High-pitched inspiratory wheeze requiring medical
intervention Kriner and colleagues [8] 2005 462 20 4.3 Inspiratory grunting, whistling or wheezing requiring
medical intervention within 24 hours after extubation Ding and colleagues [28] 2006 51 4 7.8 High-pitched inspiratory wheeze associated with
respiratory distress
Jaber and colleagues [30] 2003 112 13 12 High-pitched inspiratory wheeze requiring medical
intervention Cheng and colleagues [3] 2006 43 13 30.2 High-pitched inspiratory wheeze requiring medical
intervention (in control group of intervention arm with positive cuff leak test)
Laryngeal edema
Francois and colleagues [6] 2007 343a 76 22 Stridor with respiratory distress with need for medical
intervention (minor) or severe respiratory distress needing reintubation <24 hours after extubation (major)
Darmon and colleagues [4] 1992 663 28 4.2 Laryngeal dyspnea and/or stridor (minor laryngeal
edema) or the need for reintubation due to laryngeal edema as confirmed by endoscopy (major laryngeal edema)
de Bast and colleagues [36] 2002 76 8 11 Stridor with respiratory distress requiring reintubation
within 24 hours, confirmed by fiberoptic examination or direct view
Chung and colleagues [55] 2006 95 35 36.8 Near total occlusion of the airway as seen on video
bronchoscopy
aPlacebo group
Trang 4Figure 2
Incidence of reintubation and mortality
Table 2
Risk factors for extubation complications
Laryngeal injury Colice and colleagues [2] 1989 Persistent laryngeal neuromotor activity, tracheostomy
Kastanos and colleagues [17] 1983 Severe respiratory failure, high cuff pressure, duration of endotracheal
intubation, secretion infection Esteller and colleagues [19] 2005 Longer duration of intubation, tracheostomy, number of days in the intensive
care unit Laryngeal edema Darmon and colleagues [4] 1992 Duration of intubation (>36 hours), gender (female)
Francois and colleagues [6] 2007 Trauma at admission, gender (female), short duration of intubation
(<7 days), smaller height to tube diameter ratio, absence of methylprednisolone pre treatment
Post-extubation stridor Cheng and colleagues [3] 2006 Gender (female), lower Glasgow coma score, nonsedation treatment
Sandhu and colleagues [26] 2000 Duration of intubation (>3 days) Daley and colleagues [9] 1996 Tracheostomy, time to reintubation
Ho and colleagues [7] 1996 Gender (female) Jaber and colleagues [30] 2003 High SAPS II, medical patients, difficult intubation, history of self-extubation,
prolonged intubation, high cuff pressure Kriner and colleagues [8] 2005 Gender (female), duration of intubation (>6 days), ratio tube size to
laryngeal size >45%
Wang and colleagues [14] 2007 Gender (female) Maury and colleagues [25] 2004 Gender (female) Erginel and colleagues [15] 2005 Duration of ventilation (>5 days), body mass index (>26.5) Reintubation Daley and colleagues [9] 1996 Tracheostomy, post-extubation stridor
Jaber and colleagues [30] 2003 Post-extubation stridor Epstein and colleagues [1] 1997 APACHE II score, age, cardiopulmonary cause for reintubation Sandhu and colleagues [26] 2000 Duration of previous intubation (>3 days)
APACHE, Acute Physiology and Chronic Health Evaluation; SAPS, Simplified Acute Physiology Score
Trang 5Miller and Cole made the first attempts to make the cuff leak
test quantitative, by measuring the amount of air leak and
correlating the cuff leak volume to the likelihood of developing
laryngeal edema and PES They calculated the cut-off value
with the highest sensitivity and specificity [27] Almost none
of the patients with cuff leak volume >110 ml developed
PES: the specificity of this cut-off value was 99% and the
negative predictive value for absence of PES was 98% If a
leak <110 ml was present, only two-thirds of patients
developed PES – making the sensitivity 67% [27]
Different cut-off values have been reported in the literature,
but all nevertheless result in high specificity and negative
predicting values (Table 4) The results show that the
quantitative cuff leak test is an indicator of risk for the
development of PES and reintubation, rather than an
instrument to preclude the extubation attempt [36,37]
Close observation is necessary after extubation, especially in
the first hour after extubation The diagnosis of significant
laryngeal edema relies on symptoms Direct laryngoscopy
cannot be performed before extubation, due to the fact that
the endotracheal tube blocks sight of the larynx In addition,
laryngoscopy can cause unnecessary complications in
patients with respiratory failure if not performed for the
purpose of securing the airway [4,6,7] Naso-endoscopy can
be performed to inspect the larynx before and after extubation
Based on the clinical aspect of lesions identified, the severity
and expected morbidity can be estimated in experienced
hands [38] The severity of initial laryngeal pathology,
however, is not an accurate predictor for the severity of
adverse effects Although every patient with symptoms has
some degree of injury, not all injuries present clinically [2,17]
Laryngeal edema therefore remains largely a clinical diagnosis
Although post-extubation laryngeal edema is described as the
development of airway obstruction after extubation, neither a
widely accepted definition for laryngeal edema nor a
frequently used classification of severity is currently available
In the authors’ opinion, the definition and classification by
Darmon and colleagues and Francois and colleagues – who
use the terms minor and major to classify laryngeal edema –
is nevertheless useful (Table 5) [4,6]
Prevention
Prevention of laryngeal edema, and thereby decreasing the
incidence of extubation failure, is obviously desirable The
strategies for laryngeal edema prevention will now be
discussed
First, considering tube size as a risk factor, intubation with a 7
or 7.5 mm tube in males and a 6.5 mm tube in females would
be desirable A reduced endotracheal tube diameter,
how-ever, may delay weaning, potentially interfere with
broncho-scopic procedures and will increase ventilatory resistance,
making the use of smaller tube sizes not feasible
Also, several studies have reported the effect of cortico-steroids in preventing post-extubation laryngeal edema Early animal studies showed that administration of steroids reduces laryngeal edema and can prevent post-extubation laryngeal edema [39,40] Corticosteroid administration before extubation is part of the extubation protocol in some centers [4,7,41] Steroid use for 24 hours is considered safe, and no major adverse effects related to its use have been reported in a number of studies [3,6,13,16,32,42,43] Results of recent randomized controlled trials in humans, however, have been contradictory These differences may be explained by use of different types of steroids and different administration regimens Moreover, some protocols only use steroids in patients with a positive cuff leak test, thereby attempting to select patients at high risk for the development
of laryngeal edema
Three studies, including two well-described randomized controlled trials, used a single-dose regimen with steroids being administered within 1 hour before extubation All of these studies failed to show a significant effect on laryngeal edema, PES and reintubation rates [4,7,41] In contrast, a single dose of 40 mg methylprednisolone 24 hours before extubation was effective in lowering the incidence of PES and the reintubation rate in a randomized controlled trial by Cheng and colleagues [3] A significant rise in the cuff leak volume was measured 7 hours after the first steroid injection The authors suggest that steroids may have a time window before initiating an effect on laryngeal edema and should therefore
be given at least 7 hours before extubation [3] Indeed, studies that use regimens with multiple doses of steroids, starting at least 6 to 12 hours before extubation, seem to indicate the best chance of showing a preventive effect [3,6,13,16] The regimen used by Francois and colleagues is currently the most effective regimen known The regimen consists of 20 mg methylprednisolone 12 hours before
Table 3 Measurement of the cuff leak volume in mechanically ventilated patients
Before performing the cuff leak test, first suction endotracheal and oral secretions and set the ventilator in the assist control mode
With the cuff inflated, record displayed inspiratory and expiratory tidal volumes to see whether these are similar
Deflate the cuff
Directly record the expiratory tidal volume over the next six breathing cycles as the expiratory tidal volume will reach a plateau value after a few cycles
Average the three lowest values
The difference between the inspiratory tidal volume (measured before the cuff was deflated) and the averaged expiratory tidal volume is the cuff leak volume
Edited from Miller and Cole [27]
Trang 6planned extubation, which is repeated every 4 hours until
extubation [6]
The effect of a multidose steroid regimen was confirmed in a
recent meta-analysis Fan and colleagues calculated a risk
reduction of 0.19 (–0.24 to –0.15; number needed to treat, 5)
on the occurrence of laryngeal edema and of 0.04 (–0.07 to
–0.02; number needed to treat, 25) on the rate of
reintuba-tion [16] On the contrary, the effect of a single-dose regimen
used in older studies was not statistically significant in two
meta-analyses [16,44] The benefit from steroids will be
greater in patients at risk for laryngeal edema, who could be
identified with a positive cuff leak test [42] One should bear
in mind, however, that the positive predictive value of the cuff
leak test is low This may lead to an overtreatment of patients
with a false positive cuff leak test
Finally, early tracheostomy might be beneficial in patients at
risk for extubation failure due to laryngeal edema, but its exact
role so far remains unclear Early tracheostomy, however, has
been shown to lead to less laryngeal damage compared with
prolonged translaryngeal intubation [45] Nevertheless, it is impossible to predict morbidity based on the severity of laryngeal damage [17] There are no data at hand that support the use of tracheostomy as a preventive procedure in patients at risk of extubation failure due to laryngeal edema, but the procedure could be considered in selected cases
Therapy
Maintaining the airway, adequate oxygenation and relieving distress associated with obstruction are primary treatment goals Several treatment modalities, including reintubation, are available and will be discussed below
Obviously, intubation in the presence of edema obstructing the airway is life-saving, but may also prove difficult because
of impediment of vision [46] The American Society of Anaesthesiologists nowadays encourages the use of an airway exchange catheter in patients at risk for extubation failure, although evidence mainly consists of case reports and observational studies [47,48] The airway exchange catheter can be used in patients at high risk for post-extubation
Table 4
Predictive value of the cuff leak test
Cuff leak cut off Percentage Volume of tidal
NPV, negative predictive value; PPV, positive predictive value; PES, post-extubation stridor aCuff leak volume as a percentage of inspiratory or expiratory tidal volume
Table 5
Definition for minor and major laryngeal edema
Minor laryngeal edema: the presence of stridor (defined as an audible high-pitched inspiratory wheeze) and signs of respiratory distress Signs of
respiratory distress are a prolonged inspiratory phase and recruitment of accessory respiratory muscles as seen by subcostal, suprasternal or intercostal retraction
Major laryngeal edema: respiratory distress needing tracheal intubation secondary to upper airway obstruction confirmed by direct or video
laryngoscopy
Edited from Darmon and colleagues [4] and Francois and colleagues [6]
Trang 7laryngeal edema If necessary, oxygen can be given through
the catheter The catheter is inserted before extubation and
remains in situ in the post-extubation period This facilitates
guided (over-the-catheter) intubation A disadvantage of this
method is some degree of patient discomfort In our
experience this disadvantage is outweighed by far by its
advantages Since symptoms of laryngeal edema develop
early after extubation, the catheter can be removed if no
symptoms develop within approximately 1 hour after
extuba-tion (Figure 3)
Medical therapeutic strategies include systemic
adminis-tration of steroids and nebulization of epinephrine
Cortico-steroids downregulate the inflammatory response by
inhibit-ing the recruitment and action of inflammatory cells [49]
Together with a decrease in capillary vessel dilatation and
permeability, this inhibition reduces edema [39] The most
effective dose has not yet been determined We suggest a
dose of 0.5 mg/kg prednisolone intravenously per day The
effectiveness of glucocorticoids in post-extubation laryngeal edema has not been confirmed in randomized controlled trials In our experience, however, the potential benefit out-weighs the risk of adverse events Moreover, most adverse events are pharmacological effects of corticosteroids that are likely to disappear after the treatment period [50]
Furthermore, epinephrine nebulization is another potentially effective therapy Epinephrine acts through local stimulation
of α-adrenergic receptors on vascular smooth muscle cells, thereby causing vasoconstriction and decreased blood flow, which diminishes edema formation Randomized controlled trials that prove efficacy of epinephrine in post-extubation laryngeal edema in adults are again lacking Likewise, there is
no consensus about the potentially effective dosage of epinephrine nebulization A dose of 1 mg epinephrine in 5 ml normal saline has proved successful in some cases of upper airway obstruction in adults [51] Rebound edema is known
to occur and close observation is essential [52] Side effects
Figure 3
Post-extubation laryngeal edema therapy flow chart AEC, airway exchange catheter; NaCl, 0.9% saline; NPPV, non-invasive positive pressure ventilation; PES, post-extubation stridor
Trang 8can occur, especially in patients with coronary artery disease
[52]
Theoretically, non-invasive positive pressure ventilation can
help prevent reintubation due to respiratory insufficiency in
general [3,8] Evidence for benefit of non-invasive positive
pressure ventilation in laryngeal edema, however, is lacking
In a general intensive care population of patients with
respira-tory failure after extubation, Esteban and colleagues found an
increased mortality in the non-invasive positive pressure
ventilation group (25% vs 14%, P < 0.048), which can
possibly be explained by the increased time from onset of
respiratory failure to reintubation [53] The use of non-invasive
positive pressure ventilation in patients with laryngeal edema
might therefore be harmful, as laryngeal edema progresses
and further obstructs the remaining airway – making
reintu-bation more difficult, if not impossible
Helium administration can also be considered Because a
helium/oxygen mixture has a lower density than
oxygen-enriched air, airway resistance is decreased Again, there is
little evidence of its usefulness in adults with laryngeal edema
and in adults even with airway obstruction due to asthma,
largely consisting of case reports and nonrandomized trials
[54] If a helium/oxygen mixture is used, a minimum of 40% of
helium is advised in profound hypoxemia, since this amount of
helium reduces airflow resistance most effectively while not
compromising oxygenation [52]
Emergency tracheostomy is the ultimate step in severe cases
of laryngeal edema in which endotracheal intubation fails In
our hospital, elective tracheostomy has successfully been
used in a few patients with several, consecutive episodes of
extubation failure, not responding to preventive measures or
conservative therapeutic strategies
A practical flow chart on prevention and therapy of
post-extubation laryngeal edema and post-extubation failure is depicted
in Figure 3
Conclusions
Clinically relevant post-extubation laryngeal edema occurs in
up to 30% of extubated patients, and 4% of patients need to
be reintubated due to laryngeal edema Laryngeal edema
most often presents as inspiratory stridor and may be
associated with respiratory failure due to airway obstruction
Subsequent reintubation leads to increased costs, morbidity
and mortality Female gender, a relatively small tracheal
diameter or a large tube size and a long duration of intubation
have been identified as risk factors in different studies A
positive cuff leak test with leak volume <110 ml increases the
risk for development of PES and subsequent reintubation
significantly Multiple-dose regimens of corticosteroids
starting at least 12 hours before extubation can prevent the
development of laryngeal edema in patients with these risk
factors
The decision whether or not to treat laryngeal edema depends on the severity of symptoms Every patient with stridor after extubation should be monitored closely If an increase in severity of symptoms is noted, it is advised to start with nebulized epinephrine or a helium/oxygen mixture Corticosteroids might also be helpful, but sound evidence is lacking The use of non-invasive positive pressure ventilation
is not recommended since it may be harmful due to a delay in reintubation Reintubation should be considered early to secure the airway when possible The exact role of preventive
or therapeutic tracheostomy needs to be established
Competing interests
The authors declare that they have no competing interests
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